PROJECT SUMMARY This proposal describes a five-year research training program that will allow the candidate to achieve his long-term goal of becoming an independent clinically-oriented academic researcher, focusing on respiratory viral infections (RVIs) in immunocompromised (IC) hosts. His objective is to improve hematopoietic cell transplantation (HCT) outcomes by improving the understanding of RVI disease burden and the association with antibiotic use. He will apply the knowledge gained through this proposal to develop therapeutic and preventive strategies that mitigate the disease burden and complications of RVI in IC hosts. This proposal builds upon his clinical training in infectious diseases as well as epidemiologic and biostatistical methods for clinical research in this field. He provides a detailed plan to enhance his knowledge of healthcare services, molecular virology and conducting prospective studies. This proposal incorporates the expertise of an outstanding group of mentors, including experts in transplant infectious diseases, epidemiology, statistics, antimicrobial stewardship, healthcare services, and laboratory medicine, who are dedicated to ensuring the success of this project and the development of his career as an independent clinical researcher. The first aim of this proposal involves a large retrospective cohort of allogeneic HCT recipients to determine the burden of multiple (concurrent or sequential) RVIs on airflow obstruction, fungal and bacterial pulmonary infections, mortality and healthcare resource utilization after HCT. Using a multiplex quantitative PCR, he will test a hypothesis that multiple RVIs have a dose-dependent association with increased risk of these outcomes. His second aim will examine whether specific or cumulative antibiotic exposure is associated with increased risk of respiratory viral disease progression. As is the case in first aim, a large cohort of patients will allow him to analyze these relationships while adjusting for multiple clinical covariates. The third aim will characterize the incidence and disease spectrum of RVI as well as antibiotic use following new respiratory symptoms late after allogeneic HCT. Capturing data regarding RVI and antibiotic use will be optimized by utilizing home-based self-collected nasal swabs and prospective monitoring. By accomplishing the aims in this proposal, he will address critical gaps in our knowledge of the contribution of multiple RVIs to disease burden in HCT recipients and the utility of multiplex molecular testing. Given that new antiviral therapeutics and vaccines are on the horizon, understanding the relative significance of multiple RVIs will provide the rationale to develop ?multi?-target antiviral agents as well as therapeutic and preventive strategies. In addition, the clarification of the link between RVI and antibiotic use will inform optimized antibiotic strategies using viral diagnostics. Ultimately, this proposal will allow him to build a larger research program for better understanding of RVI disease burden in IC hosts and improve patient outcomes, which can then be applied to other vulnerable populations.